Characterization of functional transposable element enhancers in acute myeloid leukemia

Yingying Zeng, Yaqiang Cao, Rivka Sukenik Halevy, Picard Nguyen, Denghui Liu, Xiaoli Zhang, Nadav Ahituv, Jing Dong J. Han*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Transposable elements (TEs) have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes. Acute myeloid leukemia (AML) develops as a consequence of a series of genetic changes in hematopoietic precursor cells, including mutations in epigenetic factors. Here, we set out to study the gene regulatory role of TEs in AML. We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data. We show that a large number of TEs in general, and more specifically mammalian-wide interspersed repeats (MIRs), are more enriched in AML cells than in normal blood cells. We obtained a similar finding when analyzing histone modification data in AML patients. Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis. To functionally validate their regulatory role, we selected 19 MIR regions in AML cells, and tested them for enhancer activity in an AML cell line (Kasumi-1) and a chronic myeloid leukemia (CML) cell line (K562); the results revealed several MIRs to be functional enhancers. Taken together, our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.

Original languageEnglish
Pages (from-to)675-687
Number of pages13
JournalScience China Life Sciences
Volume63
Issue number5
DOIs
StatePublished - 1 May 2020

Funding

FundersFunder number
American Healthcare Professionals
Friends for Medicine in Israel
Max Planck
National Heart, Lung, and Blood Institute1R01HL138424
National Human Genome Research Institute
National Cancer Institute1R01CA197139, 1UM1HG009408
National Natural Science Foundation of China91329302, 91749205, 31210103916
Ministry of Science and Technology of the People's Republic of China2015CB964803, 2016YFE0108700

    Keywords

    • MIR
    • acute myeloid leukemia
    • enhancer
    • promoter
    • transposable element

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